Reversible Modulation of Aptamer-Ligand Binding in RNA Light-Up Aptamers Containing G-Quadruplex Using Chemical Stimuli.

Regulating a system in equilibrium transiently to out-of-equilibrium by using certain stimuli is the strategy used by natural biomolecules to function. Herein, we showed that the interaction of synthetic RNA aptamers, having a G-quadruplex core structure, with their corresponding ligands could be regulated from their equilibrium state to non-equilibrium state in a reversible manner using simple chemical stimuli (Ag+ and cysteine). The approach would be useful for designing aptamer regulators that work in a dynamic nucleic acid network, where a strict control on aptamer-ligand interaction is needed. In addition, to the best of our knowledge, this is the first report which shows that RNA G-quadruplexes can be disrupted by the addition of silver ions. This would be useful not only in designing RNA-based sensors or regulators but would also be useful for understanding the role of metal ions in RNA folding and catalysis.

Conformation and Morphology of 4-(NH2/OH)-Substituted l/d-Prolyl Polypeptides: Effect of Homo- and Heterochiral Backbones on Formation of ß-Structures and Nanofibers.

The relative stereochemistry of C2 and C4 in 4-substituted prolyl polypeptides plays an important role in defining the derived conformation in solution. cis-(2S,4S)-Amino/hydroxy-l-prolyl polypeptide (lC-Amp 9/lC-Hyp 9) shows a PPII conformation in phosphate buffer and a ß-structure in a relatively hydrophobic solvent, trifluoroethanol (TFE). It is now demonstrated that the homochiral enantiomeric cis-substituted d-prolyl polypeptide (dC-Amp 9/dC-Hyp 9) exhibits mirror image ß-structures in TFE. In the case of alternating heterochiral prolyl peptides, it is the trans-substituted [lT(2S,4R)-dT(2R,4S)] n prolyl polypeptide that shows ß-structures in TFE, while the cis-substituted [lC(2S,4S)-dC(2R,4R)] n prolyl polypeptide is disordered in both phosphate buffer and TFE. The results highlight the important chirality-specific structural requirements for ß-structure formation. The observed conformation in solution (circular dichroism (CD)) is also correlated with the morphology of the self-assemblies (field emission scanning electron microscopy (FESEM)), with the PPII form leading to spherical nanoparticles and ß-structures leading to nanofiber formation. The results shed light on the role of relative stereochemistry at C2 and C4 in defining the polyproline peptide conformation in solution and how different conformations drive self-assemblies of peptides toward specific nanostructures.